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Linking post-translational modifications and protein turnover by site-resolved protein turnover profiling

Author

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  • Jana Zecha

    (Technical University of Munich (TUM)
    German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ)
    Dynamic Omics, Centre for Genomics Research, Discovery Sciences, R&D AstraZeneca)

  • Wassim Gabriel

    (Technical University of Munich (TUM)
    Technical University of Munich (TUM))

  • Ria Spallek

    (Klinikum rechts der Isar, TUM
    TranslaTUM, Center for Translational Cancer Research, TUM)

  • Yun-Chien Chang

    (Technical University of Munich (TUM))

  • Julia Mergner

    (Technical University of Munich (TUM)
    Bavarian Biomolecular Mass Spectrometry Center at Klinikum rechts der Isar (BayBioMS@MRI), TUM)

  • Mathias Wilhelm

    (Technical University of Munich (TUM)
    Technical University of Munich (TUM))

  • Florian Bassermann

    (German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ)
    Klinikum rechts der Isar, TUM
    TranslaTUM, Center for Translational Cancer Research, TUM)

  • Bernhard Kuster

    (Technical University of Munich (TUM)
    German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ)
    Bavarian Biomolecular Mass Spectrometry Center (BayBioMS), TUM)

Abstract

Proteome-wide measurements of protein turnover have largely ignored the impact of post-translational modifications (PTMs). To address this gap, we employ stable isotope labeling and mass spectrometry to measure the turnover of >120,000 peptidoforms including >33,000 phosphorylated, acetylated, and ubiquitinated peptides for >9,000 native proteins. This site-resolved protein turnover (SPOT) profiling discloses global and site-specific differences in turnover associated with the presence or absence of PTMs. While causal relationships may not always be immediately apparent, we speculate that PTMs with diverging turnover may distinguish states of differential protein stability, structure, localization, enzymatic activity, or protein-protein interactions. We show examples of how the turnover data may give insights into unknown functions of PTMs and provide a freely accessible online tool that allows interrogation and visualisation of all turnover data. The SPOT methodology is applicable to many cell types and modifications, offering the potential to prioritize PTMs for future functional investigations.

Suggested Citation

  • Jana Zecha & Wassim Gabriel & Ria Spallek & Yun-Chien Chang & Julia Mergner & Mathias Wilhelm & Florian Bassermann & Bernhard Kuster, 2022. "Linking post-translational modifications and protein turnover by site-resolved protein turnover profiling," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27639-0
    DOI: 10.1038/s41467-021-27639-0
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